OBJECTIVE: To quantify Nectin-4 expression in tumour lesions using the Nectin-4-binding peptide Gallium-68-N188 and positron emission tomography (PET)/computed tomography (CT) in patients with advanced or metastasised urothelial cancer eligible for therapy with the Nectin-4-directed antibody-drug conjugate enfortumab vedotin, in combination with checkpoint inhibitor pembrolizumab (Ev/P).

METHODS: In 10 patients, Nectin-4 PET/CT imaging was analysed before planned systemic therapy with Ev/P based on standardised uptake value (SUV) measurements and the results were correlated to available microscopic findings on Nectin-4 immunohistochemistry and to clinical follow-up.

RESULTS: Nectin-4 PET is suitable for detecting Nectin-4 expression in tumour lesions and demonstrates heterogeneity in Nectin-4 expression - for example, between lymph node metastases and organ metastases. PET imaging of Nectin-4 expression is therefore a potentially clinically relevant method for managing the application of Nectin-4-targeted therapies.

CONCLUSIONS: We show, as a proof of principle, that Nectin-4 expression can be detected on imaging and serves as an innovative biomarker for targeted therapy in urothelial cancer. Intra-individual heterogeneous expression of Nectin-4 in metastatic sites is frequent.